Supplementary Material for: Validation of Surrogates of Urine Osmolality in Population Studies

<p><b><i>Background:</i></b> The importance of vasopressin and/or urine concentration in various kidney, cardiovascular, and metabolic diseases has been emphasized recently. Due to technical constraints, urine osmolality (U<sub>osm</sub>), a direct reflect of urinary concentrating activity, is rarely measured in epidemiologic studies. <b><i>Methods:</i></b> We analyzed 2 possible surrogates of U<sub>osm</sub> in 4 large population-based cohorts (total <i>n</i> = 4,247) and in patients with chronic kidney disease (CKD, <i>n</i> = 146). An estimated U<sub>osm</sub> (eU<sub>osm</sub>) based on the concentrations of sodium, potassium, and urea, and a urine concentrating index (UCI) based on the ratio of creatinine concentrations in urine and plasma were compared to the measured U<sub>osm</sub> (mU<sub>osm</sub>). <b><i>Results:</i></b> eU<sub>osm</sub> is an excellent surrogate of mU<sub>osm</sub>, with a highly significant linear relationship and values within 5% of mU<sub>osm</sub> (<i>r</i> = 0.99 or 0.98 in each population cohort). Bland-Altman plots show a good agreement between eU<sub>osm</sub> and mU<sub>osm</sub> with mean differences between the 2 variables within ±24 mmol/L. This was verified in men and women, in day and night urine samples, and in CKD patients. The relationship of UCI with mU<sub>osm</sub> is also significant but is not linear and exhibits more dispersed values. Moreover, the latter index is no longer representative of mU<sub>osm</sub> in patients with CKD as it declines much more quickly with declining glomerular filtration rate than mU<sub>osm</sub>. <b><i>Conclusion:</i></b> The eU<sub>osm</sub> is a valid marker of urine concentration in population-based and CKD cohorts. The UCI can provide an estimate of urine concentration when no other measurement is available, but should be used only in subjects with normal renal function.</p>